Figure 3. GPCR feedback regulation.

A) G protein switching. Upon initial stimulation, β₂AR activates the G_s protein to increase adenylate cyclase signaling and PKA activity to propagate the cellular response. PKA initiates G protein switching by phosphorylating site-specific residues on β₂AR. PKA phosphorylation of β₂AR alters the receptor coupling from G_s to G_i. Activated G_i yields a decrease in cAMP production and PKA activity. B) Arrestins partake in G_q-coupled M1 muscarinic receptor feedback regulation. Arrestin scaffolds with diacylglycerol kinases (DGKs) and recruits them to the plasma membrane. These events activate DGKs to degrade DAG, promoting arrestin-mediated G_q negative feedback regulation. C) Upon β₂AR activation, arrestin scaffolds with PDE4D and promotes its translocation to the plasma membrane. PDE4D translocation and activation negatively regulates the β₂AR-cAMP cascade by degrading the substrate necessary for PKA activation